High-dose clevudine impairs mitochondrial function and glucose-stimulated insulin secretion in INS-1E cells

<p>Abstract</p> <p>Background</p> <p>Clevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term treatment with clevudine. In this study, we investigated the effects of clevudine on mitochondrial function and insulin release in a rat clonal β-cell line, INS-1E.</p> <p>Methods</p> <p>The mitochondrial DNA (mtDNA) copy number and the mRNA levels were measured by using quantitative PCR. MTT analysis, ATP/lactate measurements, and insulin assay were performed.</p> <p>Results</p> <p>Both INS-1E cells and HepG2 cells, which originated from human hepatoma, showed dose-dependent decreases in mtDNA copy number and cytochrome c oxidase-1 (Cox-1) mRNA level following culture with clevudine (10 μM-1 mM) for 4 weeks. INS-1E cells treated with clevudine had reduced total mitochondrial activities, lower cytosolic ATP contents, enhanced lactate production, and more lipid accumulation. Insulin release in response to glucose application was markedly decreased in clevudine-treated INS-1E cells, which might be a consequence of mitochondrial dysfunction.</p> <p>Conclusions</p> <p>Our data suggest that high-dose treatment with clevudine induces mitochondrial defects associated with mtDNA depletion and impairs glucose-stimulated insulin secretion in insulin-releasing cells. These findings partly explain the development of diabetes in patients receiving clevudine who might have a high susceptibility to mitochondrial toxicity.</p

Baracle&reg; vs Baraclude&reg; for 48 weeks in patients with treatment-na&iuml;ve chronic hepatitis B: a comparison of efficacy and safety

Do Young Kim,1 Ju Hyun Kim,2 Won Young Tak,3 Jong Eun Yeon,4 Joon Hyeok Lee,5 Jung Hwan Yoon,6 Youn Jae Lee,7 Byung Seok Lee,8 Byung Hoon Han,9 Han Chu Lee10 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 2Department of Gastroenterology, Gachon University Gil Medical Center, Incheon, 3Department of Internal Medicine, Kyungpook National University Hospital, Daegu, 4Department of Internal Medicine, Korea University Guro Hospital, Seoul, 5Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 6Department of Internal Medicine, Seoul National University Hospital, Seoul, 7Department of Gastroenterology, Inje University Busan Paik Hospital, Busan, 8Department of Gastroenterology, Chungnam National University Hospital, Daejeon, 9Department of Gastroenterology, Kosin University Gospel Hospital, Busan, 10Department of Internal Medicine, Asan Medical Center, Ulsan University, Seoul, Republic of Korea Background and objective: Entecavir (ETV) is a standard of care for chronic hepatitis B (CHB). In a bioequivalence study, ETV from Dong-A ST (Baracle&reg;) was found to have a pharmacokinetic profile equivalent to ETV from Bristol-Myers Squibb (BMS) (Baraclude&reg;). The present study was conducted to evaluate the antiviral activity and safety of ETV from Dong-A ST in comparison to ETV from BMS in patients with CHB. Methods: In this multicenter, double-blind, active-controlled, stratified-randomized, parallel group, comparative trial, 118 treatment-na&iuml;ve patients with CHB were randomly assigned to receive either 0.5 mg of ETV from Dong-A ST or ETV from BMS once daily for 48 weeks. The primary efficacy endpoint was virologic improvement (a mean reduction from baseline in serum HBV DNA levels) at 24 weeks. Secondary efficacy endpoints included a mean reduction in serum HBV DNA levels at 48 weeks, proportion of patients with undetectable levels of serum HBV DNA, rates of hepatitis B e antigen (HBeAg) loss and seroconversion, rates of HBsAg loss and seroconversion, and rates of normalization of alanine aminotransferase (ALT) levels. Results: From baseline to week 24, HBV DNA levels (log10) decreased by 4.81 and 4.63 with ETV from Dong-A ST and with ETV from BMS, respectively. The upper limit of two-sided 95% confidence intervals (CI) (equivalent to one-sided 97.5% CIs) for the difference between the treatment groups was 0.208, which was below the noninferiority margin of 1, thus supporting the noninferiority of ETV from Dong-A ST in comparison to ETV from BMS. No statistically significant differences were noted between the treatment groups in all secondary and tertiary efficacy endpoints. Safety profiles were also similar between the two groups. Conclusion: In patients with previously untreated HBeAg-positive or negative HBV infection, the efficacy of ETV from Dong-A ST was noninferior to that of ETV from BMS, and there were no significant differences in efficacy or safety between two groups. Keywords: chronic hepatitis B, generic, ETV from Dong-A ST (Baracle&reg;

Pain self-efficacy and catastrophizing.sav

This is part of a dataset from a cross-sectional study on chronic pain in community-dwelling Chinese older adults

A randomized, double-blind, multicenter phase 3 study of brivanib versus placebo as adjuvant therapy to trans-arterial chemoembolization in patients with unresectable hepatocellular carcinoma: initial results

The 7th Annual Conference of the International Liver Cancer Association (ILCA), Washington, D.C., USA, 13-15 September, 2013Oral Communications, Saturday 14 September, 2013, 0-022link_to_OA_fulltex

Phase 3, randomized, double-blind, dummy-controlled, trial of radiofrequency ablation (RFA) + lyso-thermosensitive liposomal doxorubicin (LTLD, Thermodox), for hepatocellular carcinoma (HCC) lesions 3-7 cm

Oral Communications, Saturday 14 September, 2013, 0-021link_to_OA_fulltex